Telemonitoring in heart failure management: what is needed to make it fit for routine use?






Christian ZUGCK,MD
Specialist in Internal Medicine
Cardiology, Angiology, and Intensive Care Medicine
and Medical Director of the Cardiac Catheterization
Laboratory at Bogen Hospital
and Fellow of the European Society of Cardiology
and Group Practice for Internal Medicine
Steiner Thor, Straubing
GERMANY

Telemonitoring in heart failure management: what is needed to make it fit for routine use?


by C. Zugck, Germany



In parallel to the increasing complexity of medical and device therapy in chronic heart failure, patients in need of treatment are growing older. Specifically in the case of deterioration of cardiac function and symptoms of heart failure, evaluation of heart failure status may differ between subjective assessment of well-being and assessment based on objective parameters. Advances in telemonitoring may offer an opportunity to help rebalance the continuously growing health economic burden. Current concepts of telemonitoring in heart failure include measurement of weight, vital signs, and concentrations of B-type natriuretic peptide, as well as changes in intrathoracic impedance and in pulmonary artery and left atrial pressures. The importance of remote monitoring in patients with cardiac implantable electronic devices is already positively addressed in current European guidelines. However, clear interpretation of studies on noninvasive telemonitoring has been hindered by nonstandardized definitions of end points and by the lack of end point definitions specific enough to describe successful disease management through telemedical intervention. Although 2 meta-analyses have demonstrated an overall beneficial effect of telemedicine over usual care in patients with chronic heart failure, 2 large randomized trials did not confirm former positive results. Subsequently, today’s international guidelines do not state a clear recommendation for telemedical support. Despite these limitations, telemonitoring has the potential to improve heart failure care in various ways, most importantly by improving quality of life and by reducing cardiovascular morbidity and mortality.

Medicographia. 2015;37:202-207 (see French abstract on page 207)



Generally speaking, telecardiology is one of the most advanced fields in telemedicine. Looking back to Willem Einthoven’s first description of the successful transmission of a single-lead electrocardiogram (ECG) over a telegraph line in 1906, manydecades would pass before the importance of telemonitoring in heart disease would surface again. Today, over a century later, state-of-the-art medical device technology for heart disease facilitates communication between patients and caregivers. Specifically, in the case of chronic heart failure, telemonitoring can contribute to timely diagnostic and therapeutic measures. A number of concurrent developments such as demographic change in industrialized countries and revolutionary improvements in cardiovascular diagnostics, therapy, and medical device technology—specifically in regard to hypertension and coronary heart disease in recent years—can be implicated in the clearly growing number of heart failure patients.1 Indeed, current data of the German population estimate there are more than 1.8 million inhabitants suffering from chronic heart failure. Put in other numbers, every tenth inhabitant over 65 years of age is affected and approximately 200 000 to 300 000 cases are newly diagnosed every year.2 Other population-based statistics such as those for the United States reveal similarly increasing numbers.3,4 In Germany alone, the cost of heart failure treatment is approximately €3 billion per year. Advances in telemonitoring of these patients may provide an opportunity to help rebalance the continuously growing health economic burden. The development of efficient and secure information/communication technology and the growing use of Internet-based platforms enable a broad spectrum of telemonitoring methods to surface. The present article reviews current concepts of telemonitoring in the field of heart failure, all carrying the potential to improve medical caregiving in various ways and thus, ideally, reducing morbidity and mortality in heart failure.

Perspectives for telemonitoring in heart failure

Subjective assessment and objective surveillance parameters
Specifically in the case of deterioration of cardiac function and symptoms of heart failure, evaluation of heart failure status may differ between subjective assessment of well-being and assessment based on objective parameters. In daily practice, relying on patients’ subjective perception of clinical symptoms may therefore not be sufficiently reliable to detect cardiac decompensation at an early stage. For many of these patients, recurrent in-hospital treatment may seem unavoidable. The starting point of heart failure treatment strongly depends on the patient´s venue of “usual care.” Clinical practices and therapeutic regimens may differ between medical specialties, individual physicians, and even sexes. In addition, the accessibility of dedicated heart failure clinics and patient education activities depends on regional circumstances.





Current concepts of telemonitoring in heart failure include measurement of weight, vital signs, and concentrations of B-type natriuretic peptide, as well as changes in intrathoracic impedance and in pulmonary artery and left atrial pressures. The relationship between these objective parameters and the clinical situation, however, may be quite complex and prone to interference due to cofactors. For example, in some patients, significant weight gain may not always correlate with fluid retention or can occur slightly delayed to decompensation. Understandably, there are limits to any single parameter applied as a surrogate for imminent cardiac decompensation.

A classification of telemedicine in heart failure proposed by Anker et al in 2011 describes 4 generations of noninvasive telemonitoring strategies (Figure 1, page 204)5 and thus does not touch upon the use of remote monitoring via cardiac implantable electronic devices.

Appropriate end point definitions in telemonitoring studies
Current studies on heart failure management with use of telemonitoring are discussed in detail further below. So far, clear interpretation of these studies has been hindered by nonstandardized end point definitions and by the lack of those specific enough to describe successful disease management through telemedical intervention. Undoubtedly, frequent hospitalizations are a relevant health economic burden and inhospital care due to heart failure is an important marker of disease deterioration. However, counting hospital admissions in order to measure clinical success of telemonitoring may not accurately reflect the whole situation.

The primary choice of applicable end points and the appropriate interpretation of study results depend largely on the design and duration of the individual study. Contemporary time-to-event outcome analysis can therefore be misleading. Indeed, an analysis of time to first hospitalization for heart failure or cardiovascular death would suggest that a patient who had an early, short rehospitalization and perhaps no further hospitalization afterwards would have a worse outcome than a patient who died just some time later, which is clearly not the case. Hence, novel methods of comparison carrying the potential to reveal the true impact of hospitalization on the clinical status of heart failure patients are warranted. It is conceivable that patients who receive telemonitoring or other measures of intensified care may even be hospitalized more often, though quite possibly in a less symptomatic stage and ideally with a shorter length of stay than patients who are hospitalized acutely in a very critical situation.


Figure 1
Figure 1. Proposal for classification of telemedicine in heart failure.

Abbreviations: ECG, electrocardiogram; GP, general practitioner; HF, heart failure; TMC, telemedical center.
Based on reference 5: Anker et al. Lancet. 2011;378(9792):731-739. Courtesy of Koehler F.



From another perspective, hospitalization is often accompanied by the chance to escalate medical therapy, optimize medical device therapy, offer novel patient education programs, or discuss candidacy for cardiac transplantation. Surely, the definition of success of adjunct telemonitoring in heart failure is still in the concept stage and its decisive role will remain open to discussion for some time yet.

Of note, “days alive and out of hospital” represents one of the newer clinical end points used in statistical analysis of outcome in chronic diseases such as chronic heart failure. In comparison with contemporary time-to-event measures, the end point “days alive and out of hospital” incorporates both the number and the duration of multiple rehospitalizations. Further advantages are that it allows for greater emphasis on mortality and may reveal significant variations in treatment.

The section below summarizes the current evidence in telemonitoring for improving adherence to treatment and for predicting and preventing disease progression in heart failure.

Clinical studies for noninvasive use of telemedicine in heart failure

In 2005, the TEN-HMS study (Trans-European Network – Home-Care Management System) was the first larger study that analyzed the role of telemonitoring in selected patients with heart failure.6 TEN-HMS was a 3-arm, prospective randomized study in which patients included had a recent admission for heart failure, a left ventricular ejection fraction (LVEF) under 40%, persisting symptoms of heart failure, the need for diuretic therapy, and at least 1 predefined additional marker of higher risk, such as an LVEF under 25% or treatment with furosemide at a dosageof greater than or equal to100 mg/day. In total, 426 patients were assigned randomly to telemonitoring, nurse telephone support, or usual care in a 2:2:1 ratio.

Telemonitoring enabled data transfer (weight, blood pressure, ECG) via a conventional telephone line to a central Web server and then via secure intranet connections to a workstation based at each investigator site. Patients were asked to transfer data twice daily. Values greater than or less than predefined limits were signaled automatically to study nurses who could provide advice to the patient directly or, in more severe cases, first inform the primary care physician.

In addition to usual care, patients in the group with nurse telephone support were able to contact the heart failure–specialist nurse by telephone at any time during office hours. Additionally, the nurse contacted the patients by telephone each month in order to assess their symptoms and current medication and to provide advice. In comparison with usual care alone, mortality and rehospitalization rates were lower in the groups receiving either telemonitoring or nurse telephone support, with no significant differences between both these intervention groups. Of note, the duration of hospital stay and therefore the time until outpatient care was sufficient was 6 days shorter in the group of patients receiving telemonitoring.

A number of other studies, such as HOME-HF (Evaluation of Patients With Heart Failure Using Home Telemonitoring)7 and HHH (Home or Hospital in Heart failure)8 have described similar benefits of telemonitoring in heart failure in regard to the frequency and duration of hospitalizations and contacts with emergency services due to recurrent decompensation.

Bringing together the available data, 2 meta-analyses demonstrated an overall beneficial effect of telemedical intervention over usual care in patients with chronic heart failure.5,9,10 A Cochrane Collaboration meta-analysis published in 2011 described the advantage of telemonitoring in heart failure in respect to reducing overall mortality by 44% and hospitalizations by 21%.9 However, the variable methodological quality between studies and small study populations limited data interpretation.

In contrast, 2 large, prospective randomized trials: Tele-HF (Telemonitoring to improve Heart Failure outcomes)11 and TIM-HF (Telemedical Interventional Management in Heart Failure)12 did not confirm former positive results.

Tele-HF randomized 1653 patients to either telemonitoring with use of a commercially available system (Tel-Assurance, Pharos Innovations, USA) or usual care. Telemonitoring operated on the basis of toll-free calls to an interactive voice response system that questioned general health, heart failure symptoms, and body weight daily and signs of depression once a month. Clinicians reviewed patients’ answers on business days and patients whose data indicated worsening of heart failure were contacted. Individual contact with nurses or doctors by telephone was not provided. In Tele-HF, telemonitoring with use of the automated Tel-Assurance did not improve outcomes. The primary end point defined as all-cause hospital readmission or death within 180 days was achieved in a comparably high number of patients (52.3% in the telemonitoring group and 51.5% in the group receiving usual care; P=0.75). Furthermore, death rates did not differ between groups.11

The TIM-HF trial equally randomized 710 patients suffering from heart failure in New York Heart Association (NYHA) functional class II or III and an ejection fraction less than or equal to 35% to 2 groups—the first receiving usual care and the second receiving a portable device with which they could transfer data on weight, blood pressure, and ECG via Bluetooth to a telemedical service center. In comparison with earlier concepts, the telemedical center provided physician-led medical support 24 hours per day, 7 days per week for the entire study period. Furthermore, the telemedical center contacted the patient’s local physician at least every 3 months and an emergency system was integrated in accordance with standard operating procedures. Follow-up duration was 12 months minimum; mean follow-up was 26 months. All-cause mortality constituted the primary outcome. The main secondary outcome measure was cardiovascular death or hospitalization due to worsening of heart failure. Patients in both study arms had optimized medical therapy (angiotensin-converting enzyme [ACE] inhibitors, 96.6% versus 94.1%; β-blockers, 92.% versus 93.0%; aldosterone antagonists, 65.3% versus 63.2% in the usual care group versus the telemonitoring group, respectively). Compliance with daily data transfers was high (>70%). In regard to the primary and secondary outcome measures, no significant effect of telemonitoring was detected.12

To summarize the 2 aforementioned trials, in comparison with usual care and medical therapy, both randomized studies were unable to detect a significant reduction in all-cause mortality or rehospitalization in the group receiving telemedical intervention as an adjunct to usual care. However, the study design and population of both trials require critical analysis.

In the Tele-HF trial, the concept of data transfer for weight and symptoms to an automated speech recognition system was hardly made use of by most study patients and in itself does not represent today´s perception of telemedical care. For the case of the TIM-HF trial, body weight, blood pressure, and a 3-lead ECG were transmitted on a daily basis; however, requirement for study patient enrolment included fully optimized and guidelines-adherent therapy before initiation of telemonitoring. The high percentage of patients with implantable cardioverter defibrillators (>40%) may be reflected in the low mortality rate (<8% per year) in this study as well. Unfortunately, such pronouncedly optimized drug and device therapy in patients who additionally were cared for by a cardiologist every 3 months, as in the TIM-HF study, does not reflect “real-world” medical care in heart failure. This preoptimized situation may, however, explain why the TIM-HF study did not reveal an additional benefit of telemonitoring and the very low occurrence of end points in the overall cohort. Subgroup analysis showed a significant benefit of telemonitoring in certain cohorts, such as those patients who suffered decompensated heart failure in the past. These promising results in subgroups lead to the initiation of the TIM-HF II study (Telemedical Inter ventional Management in Heart Failure II). This ongoing trial is assessing 1500 patients with chronic heart failure (NYHA class II or III), an LVEF less than or equal to 45% or greater than 45%, a minimum of 1 diuretic in permanent medicinal therapy, and a previous hospitalization due to decompensated heart failure within the last 12 months before randomization. All participants will continue to receive usual care from their general practitioner and specialist and will undergo a checkup every 3 months. Half of the patient cohort will be randomly allocated to daily telemonitoring (weight, blood pressure, and heart rate). The primary end point of this study is “days lost due to unplanned cardiovascular hospitalization or death.”13

Implantable sensors

Novel concepts to measure physiological signs of disease progression, such as increasing pulmonary artery pressures measured directly with implantable monitors, may complement the current strategy of external, remote telemonitoring. In the CHAMPION trial (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA class III Patients), tailored therapy according to pulmonary artery pressures was associated with a 39% reduction in heart failure hospitalizations.14 Furthermore, the HOMEOSTASIS study (Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients) described improved hemodynamics, symptoms, and outcomes in patients at high risk for recurrent decompensation who, in addition to usual care and under guidance from a heart failure team, self-adjusted their diuretic therapy according to the measurements of an implanted left atrial pressure sensor.15

Timely prognostication of upcoming decompensation may also be provided by certain cardiac resynchronization therapy defibrillator (CRT-D) devices, which also have the functionality to monitor fluid index and patient activity. In the PARTNERS HF study (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure), a combined algorithm was used to detect which patients of the 694 included fulfilled predefined criteria for higher risk. The criteria included long atrial fibrillation duration, rapid ventricular rate during atrial fibrillation, high fluid index, low patient activity, abnormal autonomics (increased heart rate at night or low heart rate variability), and device therapy. The algorithm required at least 2 abnormal parameters to be considered positive. The results revealed that those patients who had positive combined heart failure device diagnostics had a 5.5-fold increased risk of heart failure hospitalization with pulmonary signs or symptoms within the next month. Thus, the study suggested that regarding subsequent events, diagnostics driven by CRT-D device data may stratify heart failure patients into high- and low-risk groups.16

Guideline recommendations

Due to sufficient evidence available, the importance of remote monitoring in patients with cardiac implantable electronic devices is already positively addressed in current European guidelines (European Society of Cardiology [ESC] class IIa, Level A17). Of note, this current article focuses on the use of noninvasive telemonitoring techniques in heart failure. According to the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2009 and 2013 heart failure guidelines, postdischarge systems of care, such as telecommunication, should be used to support the transition to effective outpatient care. However, the American guidelines summarize current evidence for the individual components of heart failure management such as home-based care,18,19 disease management,20 and remote telemonitoring programs as mixed and comment that the quality and cost-effectiveness of such programs require further evaluation. Similarly, though acknowledging the data from a meta-analysis of randomized controlled trials supporting the reduction in hospitalizations, the ESC/ESC-Heart Failure Association (ESC-HFA) guidelines do not state a clear recommendation for telemedical support.17 The European guidelines argue that only a few individual randomized controlled trials have shown this benefit, and thus the evidence is not robust enough to support a guideline recommendation.

Conclusion

While the complexity of medical and device therapy in chronic heart failure is increasing, patients in need of treatment are also growing older. Contemporary evaluation measures often fail to early identify those critical heart failure patients at risk for worsening of heart failure. Hospitalization is therefore common after heart failure diagnosis. The economic burden is not limited to the cost of health care services and medications, but includes lost productivity of patients and family caregivers as well. These developments may lead to difficulties in the optimal implementation of guideline specifications in daily practice. Individualized patient care seems, therefore, inevitable. From these aspects, telemonitoring may be beneficial in both the acute posthospitalization, or “bridge-to-stability” phase, and in long-term care in order to establish close and long lasting control of clinical stability. Numerous nonstandardized definitions including those that have defined the specific elements of telemonitoring and optimal patient cohorts in need of support and those that have defined clinical success have been the main limitations so far. This issue has subsequently made the appropriate interpretation of data and the transfer to guideline recommendations difficult. Despite these limitations, current data point toward the potential of telemonitoring to improve heart failure care in various ways, most importantly by improving quality of life and by reducing cardiovascular morbidity and mortality.

References
1. Cleland JG, Swedberg K, Follath F, et al; Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The EuroHeart Failure survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J. 2003;24(5):442-463.
2. Statistisches Bundesamt Deutschland. Gesundheitswesen, Anzahl der Gestorbenen nach Kapiteln der ICD-10. 2004. http://www.destatis.de/basis/d/gesu/ gesutab19.htm.
3. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics— 2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117(4):e25-e146.
4. Cubbon RM, Gale CP, Kearney LC, et al. Changing characteristics and mode of death associated with chronic heart failure caused by left ventricular systolic dysfunction: a study across therapeutic eras. Circ Heart Fail. 2011;4(4):396- 403.
5. Anker SD, Koehler F, Abraham WT. Telemedicine and remote management of patients with heart failure. Lancet. 2011;378(9792):731-739.
6. Cleland JG, Louis AA, Rigby AS, Janssens U, Balk AH. Noninvasive home telemonitoring for patients with heart failure at high risk of recurrent admission and death: the Trans-European Network-Home-Care Management System (TEN-HMS) study. J Am Coll Cardiol. 2005;45(10):1654-1664.
7. Dar O, Riley J, Chapman C, et al. A randomized trial of home telemonitoring in a typical elderly heart failure population in North West London: results of the Home-HF study. Eur J Heart Fail. 2009;11(3):319-325.
8. Mortara A, Pinna GD, Johnson P, et al. Home telemonitoring in heart failure patients: the HHH study (Home or Hospital in Heart Failure). Eur J Heart Fail. 2009;11(3):312-318.
9. Inglis SC, Clark RA, McAlister FA, Stewart S, Cleland JG. Which components of heart failure programmes are effective? A systematic review and meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of chronic heart failure management in 8323 patients: Abridged Cochrane Review. Eur J Heart Fail. 2011;13(9):1028-1040.
10. Klersy C, De Silvestri A, Gabutti G, Regoli F, Auricchio A. A meta-analysis of remote monitoring of heart failure patients. J Am Coll Cardiol. 2009;54(18): 1683-1694.
11. Chaudhry SI, Mattera JA, Curtis JP, et al. Telemonitoring in patients with heart failure. N Engl J Med. 2010;363(24):2301-2309.
12. Koehler F, Winkler S, Schieber M, et al. Impact of remote telemedical management on mortality and hospitalizations in ambulatory patients with chronic heart failure: the telemedical interventional monitoring in heart failure study. Circulation. 2011;123(17):1873-1880.
13. Charite University, Berlin, Germany; German Federal Ministry of Education and Research University of Leipzig. Telemedical Intervention Management in Heart Failure II (TIM-HF II). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Updated June 17, 2014. Available from: http://clini caltrials.gov/show/NCT01878630. NLM Identifier: NCT01878630.
14. Abraham WT, Adamson PB, Bourge RC, et al. Wireless pulmonary artery hemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011;377(9766):658-666.
15. Ritzema J, Troughton R, Melton I, et al. Physician-directed patient self-management of left atrial pressure in advanced chronic heart failure. Circulation. 2010;121(9):1086-1095.
16. Whellan DJ, Ousdigian KT, Al-Khatib SM, et al. Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) study. J Am Coll Cardiol. 2010;55(17):1803-1810.
17. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14(8):803-869.
18. Stewart S, Marley JE, Horowitz JD. Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a randomised controlled study. Lancet. 1999;354 (9184):1077-1083.
19. Stewart S, Pearson S, Horowitz JD. Effects of a home-based intervention among patients with congestive heart failure discharged from acute hospital care. Arch Intern Med. 1998;158(10):1067-1072.
20. Faxon DP, Schwamm LH, Pasternak RC, et al. Improving quality of care through disease management: principles and recommendations from the American Heart Association’s Expert Panel on Disease Management. Circulation. 2004; 109(21):2651-2654.


Keywords: chronic heart failure; device therapy; therapy optimization